GUIDELINES FOR THE USE OF ARIPIPRAZOLE LONG-ACTING INJECTION (ABILIFY MAINTENA) Introduction Aripiprazole long-acting injection (LAI)is licensed for the maintenance treatment of adult patients with schizophrenia whose condition has been stabilised with oral aripiprazole. It is not indicated for treatment-resistant schizophrenia, other conditions or for patients intolerant of oral aripiprazole. It may only be initiated by Consultant Psychiatrists following submission of the attached Named-Patient Request Form at the end of this document. Aripiprazole LAI should be administered once monthly (not 4 weekly) by the intramuscular route into the gluteal muscle. The injection site should be rotated between the two gluteal muscles. The drug is not licensed for deltoid administration. The recommended dose is 400mg once per calendar month if there are no tolerability, metabolism or interaction issues. Aripiprazole LAI does not require dose titration. However patients should be treated with 10mg to 20mg of oral aripiprazole for 14 consecutive days from the date of the first injection in order to maintain therapeutic plasma levels during the initiation period. Aripiprazole LAI is supplied in single dose packs containing a vial of powder, together with a vial of solvent and product specific syringes. These will be available from the Trusts supplier currently Lloyds Pharmacy), supplied to named individuals, following approval by the relevant Assistant Medical Director, on receipt of a valid prescription. Aripiprazole LAI is expensive compared with typical depot antipsychotics, although less expensive than higher doses of risperidone consta or paliperidone palmitate. A dose of 400mg per month costs approximately 2640 per patient year. 1. Prescribing 1.1 Patients should have a history of response and tolerability to oral aripiprazole. Patients should be stabilised on oral aripiprazole for at least 14 days before
initiating aripiprazole LAI, if they do not have a recent history of tolerability and response to the drug. 1.2 Recommended dosage regimen: 1.2.1 Switching from oral aripiprazole This should only occur in response to adherence issues in patients established on oral aripiprazole. The starting dose of aripiprazole LAI is 400mg once per month regardless of the dose of oral aripiprazole being taken, and the oral dose must be continued for 14 days from the date of the first injection. Consideration can be given to subsequently reducing the dose to 300mg per month in those patients previously stabilised on lower oral doses. 1.2.2 Switching from other antipsychotics This should normally only occur in response to lack of efficacy, intolerability or adherence issues. Switching well-stabilised patients should not normally occur as this will carry the risk of relapse. Patients should be established on oral aripiprazole for at least 14 days before being switched to aripiprazole LAI, and in addition oral aripiprazole should be continued for 14 days from the date of the first injection in order to establish therapeutic plasma levels. 1.2.3 Switching from risperidone consta or paliperidone LAI There is no manufacturer s guidance on this. Prescribers should therefore not attempt a direct switch from either of these LAI s to aripiprazole LAI. Instead patients should first be changed to oral aripiprazole, preferably for at least 14 days, stabilised and then, if there is a suitable response, changed to aripiprazole LAI as above. 1.2.4 Switching from typical depot antipsychotics There is no manufacturer s guidance on this. Prescribers should therefore not attempt a direct switch from a typical depot to aripiprazole. Instead patients should first be switched to oral aripiprazole for at least 14 days, stabilised, and then if there is a suitable response, changed to aripiprazole LAI as above. 1.3 The recommended initiation and maintenance dose is 400mg per calendar month. However a maintenance dose of 300mg per calendar month is also considered therapeutic and may be more suitable for patients who cannot tolerate higher doses or who have responded well to lower doses of oral aripiprazole. 1.4 The maximum licensed maintenance dose is 400mg per calendar month and this should not be exceeded. Doses should be scheduled once per calendar month but on no occasion should two doses be given less than 26 days apart.
It is recommended that the injection be given on a set day each month so that 12 injections are given in annually. E.g. 2nd Wednesday of each month. 2. Other dosing recommendations 2.1 Aripiprazole Lai is not licensed in patients over 65 years as efficacy and safety has not been established. In addition, the drug is not indicated for dementiarelated psychosis. The product should not be initiated in patients over 65 years, and use in patients who attain the age of 65 during the course of treatment must be kept under regular review. 2.2Aripiprazole is not licensed for use in patients under 18 years as efficacy and safety has not been established. 2.3 No dosage adjustment is required in renal impairment 2.4 No dosage adjustment is required in patients with mild to moderate hepatic impairment. Use in severe hepatic impairment should be avoided. 2.5 Dose adjustments of aripiprazole LAI in patients who are taking concomitant strong CYP2D6 inhibitors, strong CYP3A4 inhibitors, and/or CYP3A4 inducers for more than 14 days Patient taking 400mg aripiprazole LAI Strong CYP2D6 or strong CYP3A4 inhibitors Adjusted dose 300mg Strong CYP2D6 and strong CYP3A4 inhibitors CYP3A4 inducers Patients taking 300mg aripiprazole LAI Strong CYP2D6 or strong CYP3A4 inhibitors Strong CYP2D6 and strong CYP3A4 inhibitors CYP3A4 inducers 200mg Avoid use 200mg 160mg Avoid use 3. Administration 3.1 Administration of aripiprazole LAI must be by slow intramuscular injection into the gluteal muscle. (Note the ventrogluteal site is preferred to the dorsogluteal and should be used if the nurse administering is trained and competent to do so). For most patients a 38mm, 21G needle should be used. For obese (BMI>28) patients, a 50mm 21G needle should be used. 3.2 There is only one injection size available in UK 400mg/2ml. To administer smaller doses the injection must be reconstituted to produce a 400mg/2ml injection and the excess discarded. 3.3 Aripiprazole LAI requires reconstitution before use and once prepared should be administered immediately. Where immediate administration does not occur, the prepared injection may be stored in the vial below 25 C, for up to 4 hours, after which it should be safely discarded.
3.4 The starting and maintenance dose is usually 400mg per calendar month. No dose titration is required, but 10mg to 20mg of oral aripiprazole should be continued for 14 consecutive days from the day of the first injection. 3.5 Patients should be stabilised on oral aripiprazole before being started on aripiprazole LAI for at least 14 days before initiating aripiprazole LAI, if they do not have a recent history of response and tolerability to the drug. 3.6 Doses exceeding 400mg and administration of doses more frequently than once per calendar month are not licensed and should not be used. 3.7 Following administration of aripiprazole LAI there is no requirement for any enhanced level of patient monitoring. Patients should be monitored for postinjection events in the same way as for any other long-acting antipsychotic injection. 3.8 Reconstituted volumes to inject 400mg vial Dose Volume 400mg 2ml 300mg 1.5ml 200mg 1.0ml 160mg 0.8ml 3.9 Missed doses If 2 nd or 3 rd dose is missed and Action time since last injection is >4 weeks and <5 weeks The injection should be administered as soon as possible and then resume monthly injection schedule >5 weeks Concomitant oral aripiprazole should be restarted for 14 days with next administered injection and then resume monthly injection schedule If 4 th or subsequent doses are missed (i.e. After attainment of steady state) and time since last injection is: Action >4 weeks and <6 weeks The injection should be administered as soon as possible and then resume monthly injection >6 weeks Concomitant oral aripiprazole should be restarted for 14 days with next administered injection and then resume monthly injection schedule 4. Storage Packs of aripiprazole LAI should be stored in a locked drug cupboard. There is no requirement to store in a fridge 5. Cost comparison of antipsychotic long-acting injections Drug Dose Cost per year ( ) Aripiprazole LAI 400mg monthly 300mg monthly 2640 2640 Paliperidone palmitate LAI 50mg monthly 2207
Risperidone consta 75mg monthly 100mg monthly 150mg monthly 25mg two weekly 37.5mg two weekly 2939 3769 4711 2072 2894 3712 50mg two weekly Flupentixol decanoate 200mg two weekly 468 Fluphenazine decanoate 100mg two weekly 234 Haloperidol decanoate 200mg four weekly 130 Pipotiazine palmitate 200mg four weekly 624 Zuclopenthixol decanoate 500mg two weekly 182 These prices are a guideline only. The doses are not meant to be comparable with each other.
ARIPIPRAZOLE LONG-ACTING INJECTION NAMED PATIENT REQUEST FORM This form must be completed for each patient initiated on aripiprazole LAI Patient Name Date of Birth Name of Unit/Team Name of initiating Consultant Signature of Initiating Consultant Name of Community Consultant (if different from above Signature of Community Consultant Name of authorising Assistant Medical Director Signature of Assistant Medical Director I confirm that arrangements are in place for the administration of aripiprazole LAI to take place on a monthly basis in accordance with the guidelines above I confirm that the patient will be closely monitored for efficacy and tolerability, using the Glasgow Antipsychotic Rating Scale (GASS) and that a full assessment will be carried out at 3 months, 6 months and regularly thereafter, which will be documented in the patient record I confirm that the patient is non-compliant with oral medication I confirm that the patient is intolerant of typical antipsychotic depot injections Please scan and send this form to: Jon Stock Chief Pharmacist Jon.stock@kmpt.nhs.uk